Melozzo是从一个富裕的家庭，从L-ì名叫Ambrosi。他早年的事无人知晓。这只是一种假设，他是以艺术的forlivese学校形成，然后通过ansuino DA L-ì为主；都受到安德烈亚·曼特尼亚的影响。有人说，还没有确认，他成为熟练工和颜色磨床绘画大师。他的出现在1460出生地和公元前1464年首次提及.。在这期间，与Antoniazzo Romano一起，他画的壁画，在教堂的bessarione dei Santi Apostoli教堂在罗马。Melozzo后来搬到乌尔比诺，可能在1465和1474。在那里他遇到了Piero della Francesca，他深刻地影响了Melozzo的风格和使用的角度。他也会由布拉曼特和佛兰芒画家，然后工作的Federico da Montefeltro公爵工作研究架构。Melozzo可能已经与Ghent和Pedro Berruguete Justus一起装点城市的著名的公爵宫Studiolo。
在1472-74，Melozzo转移到罗马，虽然当局声称他在罗马的五年或十年，早在圣马可大教堂工作。1477他完成了他的新座位的第一部重要作品，壁画现在转移到画布上，放在thepinacoteca代表梵蒂冈，西克斯图斯四世任命白金为梵蒂冈图书馆馆员。在同一年，吉罗拉莫riariobuilt他的宫殿在罗马，现在被称为宫Altemps，设计由Melozzo。1478他对路加福音奥斯卡的原始成员，成立由西克斯图斯四世团结在城市工作的首席画家。
在1472-74，Melozzo委托Pietro Riario画在大殿dei Santi使徒罗马的半圆拱顶，他受基督升天。在这项工作中，耶稣基督大胆地和有效地缩短。这幅壁画被放在1711。基督的人物现在在Quirinal宫殿；而其他的一些部分，这影响了拉斐尔，在圣彼得在梵蒂冈博物馆大厅的圣器收藏室，Melozzo的天使和使徒的设计，是从相同的壁画。罗马时期的另一项工作是一个信号，仍然可以看到在神殿。
Melozzo的最后一个工作是在罗马一座教堂，现在被摧毁，在圣玛丽亚Trastevere的教堂。西克斯图斯四世的1484死后，Melozzo从罗马搬到Loreto。他画的壁画在圣马可教堂内della Santa Casa圣器冲天，委托枢机Girolamo巴索Della Rovere。这是一个冲天的第一个例子的装饰与建筑和人物；它极大地影响了相机的斯波西迪由M。
1489 melozzo返回罗马。这期间他可能画了一些漫画在圣海伦娜大教堂圣十字大教堂Gerusalemme教堂的镶嵌在Jesus的祝福。
Melozzo也画的嘉布遣会修士教堂冲天炉在L-ì，被1651。有人说，他执行在伟人的肖像urbinosome（Plato，但丁，西克斯图斯四世，et al）现在分巴贝里尼宫和Campana之间在巴黎集合。1493他曾在一些天花板，现在失去了，对安科纳Palazzo Comunale。Melozzo最终回到了L-ì，哪里，连同他的弟子Marco Palmezzano，他布置的FeO的教堂在圣比亚焦的教堂，二战期间被摧毁。ForlìPinacoteca民居壁画的Melozzo，被称为“pestapepe，”或胡椒研磨器，现在多损坏。原本以为是一个杂货商的标志，它是相当粗糙的现实一个精力充沛的例子，是Melozzo的世俗主题。
Melozzo于十一月去世，1494ìL-和埋在Santissima三位一体教堂（三位一体）。

而一些Melozzo的作品仍然保留，评论家们认为他对绘画艺术的进步。没有明显的作为一个调色师，他画的关心和完成，共创美好和高贵的人物。他使用透视影响其他画家。Melozzo的作品具有一定的相似性与他同时代的感言。Marco Palmezzano是melozzo瞳孔。署名“Marcus de Melotius”的Palmezzano的一些作品，随着风格一般的亲和力，使其被归因于Melozzo，后者被错误地命名为“Marco Melozzo。”melozzo绘画的强烈影响米切朗基罗，Raphael andDonato Bramante。

Melozzo was supposedly from a wealthy family named Ambrosi from Forlì. Nothing is known about his early years. It is only a hypothesis[1] that he was formed by the Forlivese school of art, then dominated by Ansuino da Forlì; both were influenced by Andrea Mantegna. It has been said, also without confirmation, that he became a journeyman and color-grinder to master painters. His presence was first mentioned in his birthplace in 1460 and again in 1464. Around this period, and together with Antoniazzo Romano, he painted frescoes in the Bessarione chapel in the Basilica dei Santi Apostoli in Rome. Melozzo then moved to Urbino, probably between 1465 and 1474. There he met Piero della Francesca, who profoundly influenced Melozzo's style and use of perspective. He would have also studied architecture by Bramante and the work of Flemish painters then working for duke Federico da Montefeltro. Melozzo may have worked with Justus of Ghent and Pedro Berruguete to decorate the studiolo of the city's famous Ducal Palace.

Around 1472-74, Melozzo transferred to Rome, although some authorities claim his presence in Rome five or ten years earlier for work in the Basilica di San Marco. In 1477 he finished his first major work in the new seat, a fresco now transferred to canvas and placed in thePinacoteca Vaticana, representing Sixtus IV Appointing Platina as Librarian of the Vatican Library. In the same year Girolamo Riariobuilt his palace in Rome, now known as Palazzo Altemps, with designs by Melozzo. In 1478 he was one of the original members of theAcademy of St Luke, founded by Sixtus IV to unite the chief painters working in the city.

In about 1472-74, Melozzo was commissioned by Pietro Riario to paint the vault of the apse in the basilica dei Santi Apostoli in Rome, his subject being the Ascension of Christ. In this work, Christ is boldly and effectively foreshortened. This fresco was taken down in 1711. The figure of Christ is now in the Quirinal Palace; while some of the other portions, which influenced Raphael, are in the sacristy of St Peter's. A hall in the Vatican Museums, with designs of angels and apostles by Melozzo, was taken from the same fresco. Another work of the Roman period is an Annunciation that can still be seen in the Pantheon.

Melozzo's last work in Rome was a chapel, now destroyed, in the church of Santa Maria in Trastevere. After the death of Sixtus IV in 1484, Melozzo moved from Rome to Loreto. There he painted the fresco in the cupola of the sacristy of San Marco in the Basilica della Santa Casa, commissioned by cardinal Girolamo Basso della Rovere. It is one of the first examples of a cupola decorated both with architectures and figures; it greatly influenced the Camera degli Sposi by Mantegna.

In 1489 Melozzo returned to Rome. During this period he probably drew some cartoons for the mosaics of Jesus blessing in the Chapel of St Helena of the basilica of Santa Croce in Gerusalemme.

Melozzo also painted the cupola of the Capuchin church at Forlì, which was destroyed in 1651. It has been said that he executed at Urbinosome of the portraits of great men (Plato, Dante, Sixtus IV, et al) which are now divided between the Barberini Palace and the Campana collection in Paris. In 1493 he worked on some ceilings, now lost, of the Palazzo Comunale of Ancona. Eventually Melozzo returned to Forlì, where, together with his pupil Marco Palmezzano, he decorated the Feo Chapel in the church of San Biagio, which was destroyed during World War II. The Pinacoteca of Forlì houses a fresco by Melozzo, known as the "Pestapepe," or Pepper-grinder, now much damaged. Originally painted as a grocer's sign, it is an energetic example of rather coarse realism and is Melozzo's only secular subject.

Melozzo died in November 1494 in Forlì and is buried in the Church of the Santissima Trinita (Most Holy Trinity).
While few of Melozzo's works are still preserved, critics agree that he contributed to the progress of pictorial art. Without being remarkable as a colorist, he painted with care and finish, creating fine and dignified figures. His use of perspective influenced other painters. Melozzo's works bear a certain resemblance to those of his contemporary Mantegna. Marco Palmezzano was a pupil of Melozzo. The signature "Marcus de Melotius" on some of Palmezzano's works, along with a general affinity of style, has led to their being ascribed to Melozzo and to the latter being incorrectly named "Marco Melozzo." The paintings of Melozzo strongly influenced Michelangelo, Raphael andDonato Bramante.