"With all due respect, that's a bunch of malarkey," Biden said at one point, during an exchange on foreign policy.
Democrats cheered his sharp tone in the only vice presidential debate. Republicans panned the vice president as disrespectful to his younger opponent.
Biden's aggressive approach stood in stark contrast to President Barack Obama's listless—and widely panned—turn on the debate stage last week. Obama, to the dismay of his supporters, clenched his jaw, looked down at his notes and held back his criticism of Republican nominee Mitt Romney.
While Biden went after him, Ryan settled on a smirk for much of the debate—his first on the national stage. He sipped water and cleared his throat through many of Biden's answers.
Voters watching at home were able to view Biden's smile and Ryan's smirk side-by-side, with most television networks broadcasting the debate on a split screen.
Early on in the wide-ranging debate on domestic and foreign policy issues, Biden leaned back his chair and gave a big grin, often audibly chuckling at Ryan. His laughter sparked a new Twitter handle called "LaughinJoeBiden."
But as the 90-minute debate pressed on, the vice president became increasingly agitated. He wagged his finger at moderator Martha Raddatz.
And walking a fine line between being aggressive and domineering, Biden started interrupting.
"Not mathematically possible," he interjected during a discussion on the budget.
But Biden didn't seem to like it much when Raddatz turned the tables on him, cutting him off during an exchange on unemployment. He spread his hands incredulously, leaned back in his chair, his arms crossed. By the end, Biden had turned serious as he talked about his Catholic faith and other issues.
So how did it play? The early reviews appeared split by party.
Republican strategist Karen Hanretty wrote on Twitter that Ryan gave Biden the "let the crazy uncle speak his mind at Thanksgiving dinner" look.
But Massachusetts Democratic Sen. John Kerry, also taking to Twitter, thought Biden was so convincing that "by the end of this, Ryan may vote for Joe."
The conservative group "Campaign To Defeat Obama" quickly sought to raise money off Biden's "rude and arrogant" performance, sending a fundraising email to supporters asking for contributions.
Obama campaign manager Jim Messina retorted: "When the other side is talking about eye rolls and smirks they are losing the debate."
Associated Press writer Beth Fouhy contributed to this report.