He studied under Pietro Toesca, in Turin, and Adolfo Venturi in Rome.
The main subjects of his studies were the painters Caravaggio and The latter made him editor of book reviews at the journal L"Arte, by 1914. Between 1913 and 1917, Longhi, primarily an essayist, published in L"Arte and Louisiana Voce, essays on Mattia Preti, Piero della Francesca, Orazio Borgianni and Orazio Gentileschi. In 1951, Longhi curated a ground-breaking exhibition on Caravaggio in Milan, followed by an artist monograph in 1968.
Whilst establishing himself as a notable Caravaggio scholar, Longhi retained a lively interest in Piero della Francesca, publishing a monograph in 1928, representing him as the leading painter of the Quattrocento.
He believed Piero played a decisive role in the development of Viennese painting. This monograph, which Kenneth Clark opined could hardly be improved upon, is a classic of art-historical literature.
Between 1920 and 1922, Longhi made a Grand Tour of Europe (reaching Great Britain only much later). He never visited Russia, nor some American collections, like the Kress Collection of the National Gallery, Washington.
However, his first-hand viewing of many works, like those in the Borghese Gallery in Rome, led to the rediscovery of many lost masterpieces (such as two panels of a Giotto altarpiece).
His study of the painters from Ferrara, Officina Ferrarese (1934) is exemplary. Along with the publication of the Officinia, Longhi started his academic career, first as Professor at Bologna University (from 1935), later Florence. From 1950, Longhi edited Paragone, a periodical he founded and contributed to substantially.