The renewed American push to defeat the Taliban-led insurgency comes nearly five years after the U.S.-led invasion ousted the hard-line militia from power.
It also follows a similar two-week long NATO operation in the country's south, which the Western military alliance said have left over 500 insurgents killed.
Fighter planes and helicopters will back ground troops in American-led Operation Mountain Fury, which aims to defeat Taliban insurgents and extend the government's reach in volatile areas close to the Pakistan border, according to the U.S. military.
The new push is "just one part of a series of coordinated operations placing continuous pressure on Taliban extremists ... in order to provide security to the population, extend the government to the people and to increase reconstruction," the military said in a statement.
The 7,000 U.S. and Afghan troops will concentrate their fight on the central and eastern provinces of Paktika, Khost, Ghazni, Paktya and Logar, military said.
Taliban and other Islamic extremist groups, including al Qaeda, are known to operate in the region, especially in the areas bordering Pakistan where the reach of the government is weak and militants find sanctuaries.
Underscoring the dangers the troops face, two separate insurgent attacks on a military base in Khost province killed a U.S.-led coalition soldier and wounded another on Friday, the military said. A number of Afghan troops were also wounded, a statement said.
A suspected suicide bomber also blew himself up in the same province when explosives strapped to his body went off prematurely as he approached a police checkpoint on Saturday. No one else was injured in the blast, police said.
The U.S. military said that troops have been preparing for weeks for Mountain Fury but launched its "maneuver phase" early Saturday.
A separate U.S.-led operation called Big Northern Wind has been going on in neighboring Kunar province's Korangal Valley since late August.