Donald B. Patterson was born July 22, 1936, in Columbus, Ohio. He started on piano as a child, absorbing Erroll Garner's records, and some of that pianistic phrasing stayed audible in his playing even after he switched instruments. In 1956 he heard Jimmy Smith play the Hammond organ and changed course, teaching himself the instrument and making his professional debut on it in 1959. Patterson worked the Philadelphia jazz and rhythm-and-blues circuit through the late 1950s and early 1960s, the same scene that produced trumpeter Lee Morgan and drummer Rashied Ali, born Robert Patterson (no relation), who has recalled moving through Philadelphia's jazz clubs alongside Lee Morgan, organist Don Patterson, and Jimmy Smith before Ali left for New York in the early 1960s and the free-jazz association with John Coltrane that defined his career. No recording of the two Patterson-and-Ali (unrelated by blood) crossing paths in a studio has surfaced; the connection is biographical, two young Philadelphia musicians working the same clubs before their careers diverged.

Patterson's break came through saxophonist Sonny Stitt, who heard him locally and made him his preferred organist; the association helped establish Patterson's name on the East Coast circuit through the early 1960s. His first Prestige session, cut March 19, 1964, was actually a Stitt date, Shangri-La, credited to "Sonny Stitt with Don Patterson," with Billy James on drums. Patterson's own leader debut followed quickly: The Exciting New Organ of Don Patterson, recorded May 12, 1964, at Van Gelder Studio with tenor saxophonist Booker Ervin and James. Prestige had him back within weeks for Hip Cake Walk (May and July 1964), and by the fall the classic working trio was in place: guitarist Pat Martino and drummer Billy James, the front line Patterson would lean on, in various combinations, for most of the next decade. Holiday Soul, a full album of Christmas material cut November 25, 1964, became his most commercially successful record, reaching number 85 on the Billboard 200 in 1967. Patterson's People (1964-65) brought Stitt and Ervin together on the same date for the only time on a Patterson-led session.

The Prestige run continued at a steady clip through the back half of the 1960s: Satisfaction! and The Boss Men (the latter a trio billing with Stitt, recorded December 28, 1965) in 1966; Soul Happening!, with guitarist Vinnie Corrao subbing for Martino, that August; Mellow Soul, a trio date with David "Fathead" Newman on tenor and flute, in May 1967; and, across 1968, Four Dimensions (with Houston Person), Opus De Don (with trumpeter Blue Mitchell and tenor saxophonist Junior Cook), and Boppin' & Burnin' (with trumpeter Howard McGhee and altoist Charles McPherson). He also turned up as a sideman during these years, most notably on the 16-year-old Eric Kloss's debut, Introducing Eric Kloss (September 1, 1965, with Martino again on guitar), and alongside organist Richard "Groove" Holmes on Kloss's Love and All That Jazz (1966). Funk You! (September 24, 1968, with Stitt, McPherson, and Martino) and Oh Happy Day (1969, with George Coleman and Houston Person) closed out the decade, followed by Brothers-4 (1969, co-billed with Stitt, with Grant Green on electric guitar) and Tune Up!, a 1971 release drawn from leftover 1964 and 1969 sessions.

Patterson's momentum stalled in the 1970s. Substance-abuse problems cut into his output, and he spent much of the decade living in Gary, Indiana, recording only occasionally, for Muse Records: The Return of Don Patterson (recorded October 30, 1972, released 1974, with Eddie Daniels and guitarist Ted Dunbar) and These Are Soulful Days (recorded September 17, 1973, released 1974, reuniting him with Martino alongside tenor saxophonist Jimmy Heath and drummer Albert Heath). Two further Muse albums followed later in the decade, Movin' Up! (1977, with altoist Richie Cole and guitarist Vic Juris) and Why Not... (1978, produced by Houston Person, with tenor saxophonist Bootsie Barnes and drummer Idris Muhammad) - his last studio dates as a leader.

In the 1980s Patterson relocated to Philadelphia and mounted a modest comeback, but his health was failing by then. He died in Philadelphia on February 10, 1988, at age 51.

Patterson was one of the most bop-rooted players to come out of the 1960s Hammond B-3 boom: he could sit inside a bluesy, riff-based soul-jazz groove as comfortably as any of his organ contemporaries, then break out into long, sharply articulated bebop lines that owed as much to his early piano training and to Charlie Parker-school horn players as to the organ tradition itself. That combination made him Jimmy Smith's clearest bop-leaning heir on the instrument and, in Sonny Stitt's own estimation, his favorite organist to work with, precisely because Patterson could match a Parker-descended saxophonist's harmonic vocabulary rather than simply laying down a groove behind him. The working trio format he settled into with guitarist Pat Martino and drummer Billy James, sustained across a dozen-plus Prestige and Muse albums between 1964 and 1977, stands as one of the more durable organ-guitar-drums units of the soul-jazz era, alongside Smith's own classic trios and Jimmy McGriff's and Richard "Groove" Holmes's working groups.