In an audio speech released online a day after the 12th anniversary of the 9/11 strikes, Zawahri said attacks "by one brother or a few of the brothers" would weaken the U.S. economy by triggering big spending on security, SITE reported.
Western counter-terrorism chiefs have warned that radicalised "lone wolves" who might have had no direct contact with al Qaeda posed as great a risk as those who carried out complex plots like the 9/11 attacks.
"We should bleed America economically by provoking it to continue in its massive expenditure on its security, for the weak point of America is its economy, which has already begun to stagger due to the military and security expenditure," he said.
Keeping America in such a state of tension and anticipation only required a few disparate attacks "here and there", he said
"As we defeated it in the gang warfare in Somalia, Yemen, Iraq and Afghanistan, so we should follow it with ...war on its own land. These disparate strikes can be done by one brother or a few of the brothers."
At the same time, Muslims should seize any opportunity to land "a large strike" on the United States, even if this took years of patience.
The Sept 11, 2011 attacks, in which hijacked airliners were flown into New York's World Trade Center, the Pentagon in Washington and a Pennsylvania field, triggered a global fight against al Qaeda extremists and their affiliates. Almost 3,000 people were killed in the attacks.
In his audio speech, Zawahri said Muslims should refuse to buy goods from America and its allies, as such spending only helped to fund U.S. military action in Muslim lands. He added that Muslims should abandon the U.S. dollar and replace it with the currency of nations that did not attack Muslims.
Zawahri spoke approvingly of one of the worst attacks on U.S. soil since September 11, 2001, the bombing of the Boston Marathon in April, which U.S. authorities say was carried out by two ethnic Chechen Muslim brothers. The attack killed three people and injured 264.
Zawahri sought to paint the bombing as part of al Qaeda's violent transnational campaign of jihad or holy war against U.S. interests, even if it was relatively small-scale.
"The Boston incident confirms to the Americans ... that they are not facing individuals, organizations or groups, but they are facing an uprising Ummah (Muslim community), that rose in jihad to defend its soul, dignity and capabilities."
"What the American regime refuses to admit is that al Qaeda is a message before it was an organization," he said.
Zawahri, suspected by many security specialists to be living in the Pakistan-Afghanistan border area, added that the al Qaeda message simply was that if Muslims wanted to live in dignity and "be liberated", then they had to defend their dignity.