Poekilopleuron was named by Eudes-Deslongchamps (1837). Its type is Poikilopleuron bucklandii.

It was synonymized subjectively with Megalosaurus by Vetter (1884), Marsh (1884), Marsh (1885), Mansel-Pleydell (1888), Lydekker (1888), Zittel (1890), Woodward and Sherborn (1890), Marsh (1895), Marsh (1896), Hay (1902), Huene (1923), Romer (1956), Tatarinov (1964), Romer (1966), Steel (1970), Paul (1988); it was reranked as Megalosaurus (Poekilopleuron) by Bigot and Cardinet (1938); it was misspelled as Poikilopleuron by Huene (1909), von Zittel (1911), Huene (1914), Piveteau (1923), Nopcsa (1928), Carroll (1988), Kurzanov (1989), Allain and Chure (2002), Rauhut (2003), Holtz et al. (2004), Mateus (2006), Carrano et al. (2012), Hanson and Makovicky (2013); it was corrected as Poikilopleuron by Bakker et al. (1992), Rauhut et al. (2016).

It was assigned to Reptilia by Eudes-Deslongchamps (1837); to Lacertilia by Owen (1841); to Pleurosauri by Fitzinger (1843); to Dactylopodes by Meyer (1845); to Crocodilidae by d'Orbigny (1849); to Sauria by Quenstedt (1852); to Crocodilia by Owen (1842), Owen (1854); to Amphicoelia by Owen (1860), Owen (1861); to Goniopoda by Cope (1869); to Dinosauria by Leidy (1873); to Coelospondilia by Owen (1876); to Ornithoscelida by Williston (1878); to Plateosauridae by Huene (1909), von Zittel (1911); to Pachypodosauria by Huene (1914); to Megalosaurus by Bigot and Cardinet (1938); to Torvosauridae by Kurzanov (1989); to Megalosaurinidae by Huxley (1870), Bakker et al. (1992); to Spinosauroidea by Allain and Chure (2002); to Tetanurae by Rauhut (2003); to Megalosaurinae by Nopcsa (1928), Holtz et al. (2004); to Eustreptospondylidae by Mateus (2006); to Afrovenatorinae by Carrano et al. (2012); to Megalosauridae by Piveteau (1923), Carroll (1988), Hanson and Makovicky (2013); and to Eustreptospondylinae by Rauhut et al. (2016).