The current study demonstrates that Mcm10 forms an isolable stoichiometric complex with CMG that greatly stimulates CMG helicase activity (up to 30-fold) and enhances processivity. Strikingly, Mcm10 uniquely promotes CMG bypass of a lagging strand block without displacing it, suggesting that Mcm10 isomerizes the CMG-DNA complex either to a steric exclusion mode or by facilitating ring opening. In contrast, leading strand blocks inhibit CMG unwinding but Mcm10 helps CMG displace the blocks and continue unwinding, consistent with the idea that Mcm10 makes CMG a more powerful, processive helicase. Despite the strong stimulation of helicase activity, Mcm10 has little effect on CMG-dependent DNA synthesis by the replisome in vitro, particularly in the presence of the Mrc1-Tof1-Csm3 complex. However, the replisome becomes stalled by lagging strand blocks in the absence of Mcm10, indicating that CMG uses an internal unwinding mechanism even in the context of rapidly moving replisomes. Stalled replisomes are released by addition of Mcm10, further supporting the idea that Mcm10 functions at the level of the helicase to enhance processivity, provide additional power and to enable blocked replisomes to bypass obstacles on the DNA. These functions may also explain the role of Mcm10 in origin initiation as described in the Discussion.