Paolo Russo was born in Pescara, in Italy's Abruzzo region, in 1969. He started on piano as a child, training classically under Rachele Marchegiani, and graduated from the Conservatorio "Luisa D'Annunzio" in Pescara in 1993. In 1995 he studied piano in New York with Richie Beirach, and in 1996 he moved to Copenhagen, where he entered the soloist class of the Rytmisk Musikkonservatorium (the Danish Rhythmic Music Conservatory), graduating in 2002. He took up the bandoneon in 2001 and went on to study the instrument with the Argentine master Nestor Marconi in Buenos Aires, in 2004 and again in 2013. He has lived in Denmark ever since, most recently on the island of Mon, and has toured well beyond Europe as well, with dates in Argentina, Uruguay, Brazil, Japan, the Faroe Islands, Thailand, Tanzania, Mozambique, Algeria, Russia, the United States, Greenland and Cuba.

His first record as a leader, Oltretango (2005, Dodicilune), was credited to "Paolo Russo (3) & Band Au Neon," with Russo on bandoneon alongside pianist Francesco Cali and saxophonist Fabrizio Mandolini. Doble A(nima) followed on the same label in 2007, a solo-billed date pairing his piano and bandoneon playing, Discogs-tagged Tango and Contemporary Jazz. That same year he was the featured bandoneon soloist on Danish pianist and composer Martin Lutz's sextet album Where Are The Trumpets? (Calibrated, 2007), which won the Danish Music Award for Crossover Album of the Year in 2008.

Between 2019 and 2020 he released a trilogy of albums on the American label Odradek Records. Imaginary Soundtrack (2019) is written for an unusual quartet of bandoneon, recorder, vibraphone and double bass. Overland (2019), billed to the Paolo Russo Trio, teams him with bassist Thommy Andersson and drummer Marcello Di Leonardo, with saxophonist Fabrizio Mandolini and percussionist Bruno Marcozzi guesting; Di Leonardo, coincidentally, was also born in Pescara in 1969, the same city and year as Russo himself. Playground (2020) is a solo record on which he plays bandoneon, piano, synthesizer and percussion. An earlier session, Alchemy (2004, Splasch Records), paired his piano and bandoneon with bassist Bo Stief and saxophonists Fabrizio Mandolini and Kristoffer Rosing-Schow; it is not indexed on Discogs and its personnel is sourced from a retail listing rather than verified credits.

Beyond that Discogs-documented core, Russo has built an extensive self-released catalog, much of it centered on the bandoneon as a solo instrument: a six-volume Bandoneon Solo series (from Jazz Standards, 2015, through Bandobop), the live quintet recording Fellini Goes Jazz, cut at the 2013 Copenhagen Jazz Festival at Jazzhus Montmartre, and duo projects including Solstice with guitarist Jeppe Holst and Kattegat with an artist billed as Vilensky. In 2018 his composition "Concerto Bandoneon N.1," in three movements, won Category A of the International Composition Contest "Heinrich Band" for Bandoneon, run by Italy's Accademia Italiana del Bandoneon; he premiered the full Concerto for Bandoneon & Chamber Orchestra in November 2019. In 2024 he released MiraZen, a choral work for five voices co-created with Marianne Miravet Sorribes, on which his wife, singer Katrine Krog Russo, is one of the vocalists.

Russo has also composed for Danish television, including the sitcom Klovn (2012), and for theater and documentary film. In June 2022 he and Katrine Krog Russo opened Paolo's Jazz Club, an intimate venue on the island of Mon.

Russo's catalog sits at the meeting point of jazz, Argentine tango and Nordic and Mediterranean folk idioms, a mix his own site sums up as moving from Italian and classical roots through Nordic atmospheres and free improvisation, with an Argentine tango undertow. Every one of his Discogs-indexed leader releases is genre-tagged Jazz, and his professional jazz training runs through the Rytmisk Musikkonservatorium's soloist program and private study with the American jazz pianist Richie Beirach; the bandoneon side of his work traces instead to Nestor Marconi's tango lineage in Buenos Aires, and the two strands run together rather than in separate projects. Imaginary Soundtrack's quartet of bandoneon, recorder, vibraphone and double bass, and the Concerto for Bandoneon & Chamber Orchestra's pairing of the instrument with a classical ensemble, both favor small, unusual chamber-scale combinations over a conventional rhythm section. Reviewers have picked up on the same duality: a Musica Jazz review of the Overland trio praised the way "melodia d'italica memoria" (melody of Italian memory) serves the group's improvising, while a Jazz Journal review of Playground singled out the contrast between the "mysterious nostalgia" of his bandoneon playing and the clarity of his piano touch.