Born in São Paulo, Guilherme Lopes was a Grêmio Osasco youth graduate, and made his senior debut for the club on 1 August 2012 by starting in a 2–3 home loss against Palmeiras for the year's Copa Paulista.
On 31 January of the following year he moved abroad, signing a six-month loan deal with F.C.
[1] Guilherme Lopes made his professional debut on 7 April 2013, coming on as a late substitute for Tozé in a 2–0 home win against F.C.
He subsequently served another temporary stint at Audax Rio de Janeiro before being released.
On 6 November 2015 Guilherme Lopes signed for Independente de Limeira, after previously representing Nova Iguaçu.