Emanuele Maniscalco was born in Brescia in 1983, into what he has described as a family of music amateurs. He started piano at eight and drums at twelve, and by fourteen was already gaining local notice for playing jazz by ear at friends' houses. He is largely self-taught on both instruments, but received formal grounding after meeting saxophonist Corrado Guarino and drummer William Tononi in 2000: from 2001 to 2003 he studied Trio Performance at the Fondazione Siena Jazz under pianist Stefano Battaglia, bassist Paolino Dalla Porta and drummer Fabrizio Sferra, and continued attending Battaglia's monthly Siena workshops through 2008. He also attended a Berklee summer masterclass at Umbria Jazz in 2001.

By his early twenties Maniscalco was working steadily as a sideman on the Italian scene, and between 2004 and 2007 he toured and recorded as drummer in trumpeter Enrico Rava's "Under 21" quintet, alongside saxophonist Francesco Bigoni, pianist Giovanni Guidi and bassist Giulio Corini - a Rava-mentored young-Italian lineup confirmed by a shared 2006 studio date, Jazzitaliano Live 2006, on which Maniscalco is Discogs-credited on drums. That same year he also drummed on the Giovanni Guidi Trio's Tomorrow Never Knows and on tenor saxophonist Francesco Bearzatti's Circle, and in 2008 he recorded on bassist/trombonist Ares Tavolazzi's theater-music album Godot (E Altre Storie Di Teatro).

He began leading his own projects in 2006 with Slow Band, which released its debut album in 2010 on Re:think-Art Records, and around the same period he also recorded with the quartet From Time To Time - Francesco Bigoni (tenor saxophone), Nelide Bandello (drums) and Giulio Corini (bass), with Maniscalco on piano - for a 2011 album on the Bologna label El Gallo Rojo built entirely around compositions by Paul Motian, a musician he has repeatedly cited as a formative influence. In 2010 he also recorded as drummer on pianist Alessandro Galati's newly billed Alessandro Galati Trio album Cubicq, alongside Tavolazzi.

His profile rose internationally in 2010 when guitarist Roberto Pianca, who had previously played with Maniscalco in the band Food Chain, brought him into a new bass-less trio with Swiss reedman Nicolas Masson, later named Third Reel. The group signed to ECM Records: their self-titled debut, produced by Manfred Eicher and recorded in February 2012 at Lugano's Auditorio Radiotelevisione Svizzera, appeared in 2013 with Maniscalco on drums; a second ECM album, Many More Days, followed in 2015, this time with Maniscalco moving between piano and drums. By the mid-2010s Maniscalco had relocated to Copenhagen, Denmark, where he remains based, and folded into the city's improvised-music scene: ongoing groups and duo/trio projects there include Høbama (with organist Claus Højensgård and drummer Nelide Bandello), Il sogno, the recurring trio billed simply as Maniscalco/Bigoni/Solborg (with Francesco Bigoni and Danish guitarist Mark Solborg), and sideman work for Danish and international improvisers including guitarist Jakob Bro and vocalist Maria Faust's Sacrum Facere ensemble.

In 2016 he recorded Diminuendo for the Italian label C.A.M. Jazz, a trio session led by bassist Andrea Lombardini with French serpent and tuba player Michel Godard, on which Maniscalco is Discogs-credited on both piano and drums - one of his few subsequent studio dates for an Italian label after his move to Denmark. He has continued releasing under his own name and in shifting duo and trio configurations through the 2020s, including the solo/self-released Væver (2020) and the guitar trio The Boy Next Door (2021, with Sandro Gibellini and Giulio Corini), while also working as a photographer alongside his music career, per his own Discogs artist profile.

Maniscalco names Carla Bley, Paul Motian and Charlie Haden as his earliest compositional influences, and that lineage runs through his catalogue in concrete ways: the 2011 From Time To Time quartet album is a dedicated set of Paul Motian compositions, and Third Reel's bass-less, guitar-reeds-drums instrumentation and unhurried, conversational interplay have been repeatedly compared by reviewers to Motian's own long-running trio with Bill Frisell and Joe Lovano - a lineage Third Reel's own members have acknowledged while noting the group has "something of its own to say." Discogs' own style tags across his catalogue bear this out: Væver (2020) is tagged Avant-Garde Jazz and From Time To Time (2011) Free Improvisation, while the two ECM-era Third Reel albums sit in a more chamber-like, composition-and-space-driven register - Discogs tags the 2013 self-titled debut "Contemporary Jazz" - that reviewers have described as intimate and unhurried rather than freely abstract. Across both registers, Maniscalco moves fluidly between piano and drums, often within the same group and sometimes the same album, and gravitates toward small, bass-less or otherwise unconventionally instrumented ensembles - a working method that has stayed consistent from Third Reel through his Copenhagen-era trios.