The war-ravaged country's President Ashraf Ghani will meet key figures including US Secretary of State John Kerry, UN chief Ban Ki-moon and NATO head Jens Stoltenberg at the conference in the Belgian capital.
The meeting is expected to drum up pledges worth at least three billion dollars annually over the next four years, although the exact amount is unclear among donor fatigue caused by the war in Syria and the migration crisis.
In return the 70 donor countries and 25 organisations gathered in Brussels will expect Kabul to promise it will tackle corruption, waste, political reform and human rights.
European Union foreign policy chief Federica Mogherini said late Tuesday the Brussels conference was "dedicated to the international support to Afghanistan, and to Afghanistan's support for the Afghan people".
Almost exactly a decade and a half after the start of the US-led invasion to topple the Taliban after the 9/11 attacks, Afghanistan remains dependent on foreign aid and a limited NATO military presence to keep going.
Violence has continued with Afghan forces fighting Taliban militants in the flashpoint city of Kunduz this week while a US soldier was killed in a bomb blast during operations against Islamic State militants in the east on Tuesday.
The United States and the 28-nation EU currently each provide about a third of all international aid to Afghanistan, with Japan the next largest donor.
A State Department spokesman said the conference was a chance for Kerry and the other officials to "reaffirm our collective support for Afghanistan's development and self-reliance".
Seventy countries attending
The conference follows up from a meeting in Tokyo in 2012 where the international community agreed to provide four billion euros a year in funding until the end of 2016.
It also comes two years after the London Conference on Afghanistan at which then newly-elected president Ghani vowed to build a more self-reliant country.
On Tuesday, Ghani attended an event in Brussels on female empowerment, a key issue in an impoverished, socially conservative Islamic country.
"We cannot count our successes by the number of women in high-ranking positions, we have to measure our effort by the empowerment of millions of girls," Ghani said.
Mogherini said the conference was "dedicated to all Afghan women and their talent and their hopes and their lives".
The EU formally signed a state building contract of 200 million euros for 2017-2018 on Tuesday.
Ahead of the conference Brussels and Kabul this week also struck a tentative deal for Afghanistan to take back migrants from the EU, which faces its biggest refugee crisis since World War II.
EU officials denied reports that aid pledges would depend on Kabul accepting the return of 80,000 asylum-seekers deported from EU countries.
But a key issue in Brussels will be countering the huge waste of international aid funds that have poured into Afghanistan since 2001.
The United States has spent around $110 billion on Afghanistan's reconstruction since 2001, more than the cost of the Marshall Plan that rebuilt a devastated Europe after World War II, but with limited results.
Naeem Ayubzada, founder of NGO the Transparent Elections Foundation of Afghanistan, told AFP that in a sign of progress Afghan government officials had promised to let civil society organisations like his monitor spending more closely.
But he warned that if the Afghan government and the donors continue with the "same methods and mechanisms, the corruption will be increased".
