The U.S. side was unsurprisingly the better lot in the opening stanza, and the scoreline was nearly doubled minutes before the interval when a dancing McKennie found Nick Lima, who rifled a shot that was parried away by Clarke.
Clarke was the busiest Guyanese player at Allianz Field in the opening 45 minutes, thrice denying Gregg Berhalter's free-flowing attack as the two sides headed down the tunnel separated by a goal.
The U.S. didn't wait long to increase their advantage after the break.
Boyd was the recipient of a perfect pass over the top from Michael Bradley in the 52nd minute. The 24-year-old laced a right-footed shot into the bottom left corner, which gave the U.S. their 1000th goal all time.
Zardes made it 3-0 minutes later. Arriola crept in off the left wing and fired a rocket toward goal that deflected off a Guyana defender before it ricocheted in off the face of Zardes.
Arriola was again the architect of a profitable attack, stretching the right side of the Guyanese defense nine minutes from time before firing a pass to Boyd, who got an inch on his marker and rocketed in an effort beyond a helpless Clarke.
It was far from a fluid performance from the U.S., especially considering Guyana's willingness to make probing runs forward while sacrificing numbers at the back.
Next up for Gregg Berhalter's charges is a rematch with Trinidad & Tobago on June 22 in Cleveland. T&T famously denied the U.S. a spot in the 2018 World Cup for the first time since 1986 courtesy of a shocking 2-1 victory in October 2017.