Goals from Christian Noboa, Juan Cazares, Enner Valencia and Junior Sornoza saw Ecuador to their win at the Lockhart Stadium.
It extended Bolivia's winless run to 12 matches, and that could get worse when they face Mexico on Tuesday.
Ecuador interim coach Sixto Vizuete was without Antonio Valencia, Felipe Caicedo and Jefferson Montero.
Just how good his team's form is will be tested on Tuesday, when Ecuador face Brazil.
Winless since February 2013, Bolivia's squad was also largely inexperienced.
Noboa gave Ecuador the dream start with his third international goal in the ninth minute.
Renato Ibarra was released down the right and his cutback found Noboa, whose placed effort snuck into the bottom corner despite Bolivia goalkeeper Romel Quinonez getting a hand on the shot.
Vizuete's Ecuador were dominant, controlling possession and looking dangerous in the attacking third.
And they were deservedly rewarded with a second goal in the 34th minute.
On debut, Cazares found space on the edge of the area before striking into the top corner with a dipping, 30-yard effort.
Quinonez's positioning for the goal was questionable as he found himself yards off his line.
But the shot-stopper did well to deny Enner Valencia soon after, diving to his left to keep out a powerful long-range free-kick.
Ecuador were unlucky not to be further ahead at the break as they wasted several good opportunities to set up goalscoring chances.
Bolivia worked their way into the contest early in the second half.
But Enner Valencia sealed the win for Ecuador, getting on the end of a well-weighted Cazares pass, rounding Quinonez before finishing into an open goal.
Substitute Carlos Gruezo had a goal ruled out for offside late on, but Ecuador would get a fourth in the 84th minute.
The substitutes combined as Joao Plata teed up Sornoza to finish powerfully from the edge of the area.