Before leaving Washington, Mrs Clinton emphasised that the US administration was going to do everything to broaden and deepen Washington's engagement with India.
It is a message that India is keen to hear - during the first months of the Obama administration, as Washington focused intensely on Pakistan, Afghanistan and the fight against al-Qaeda, India worried that the US would view its policy towards the whole region through that prism.
But the focus of Mrs Clinton's visit, at least publicly, is very clearly on US-Indian ties.
Two-fold aim
American officials often make a stop in Pakistan when they visit India, but Mrs Clinton will only go to Islamabad in the autumn.
Washington is keen to dispel any doubts about its commitment to ties with Delhi that its early focus on Pakistan and Afghanistan may have given rise to.
For Washington, there is a lot riding on the visit. And in an opinion piece published in the Times of India, Mrs Clinton points out that "the world has a lot riding on our cooperation" as well.
For Mrs Clinton, the aim is two-fold.
First, she wants to convince India that the Obama administration is as keen on close ties with India as George W Bush was. The Bush administration's 2008 nuclear agreement with India ended a three decade-long ban on nuclear trade with Delhi, so Mrs Clinton will be eager to maintain the momentum.
But Mrs Clinton is also seeking a variety of tangible results while she is here.
She is hoping to sign an end-of-use monitoring agreement, which would ensure that any arms technology sold to India does not end up in third countries. This is a legal pre-requisite for any US arms sales to India.
Washington is also hoping that India will announce it has reserved two sites for US companies to build nuclear power plants, thus allowing the US to benefit from any lucrative nuclear business deals, deals that were made possible after Washington helped India end its nuclear isolation with last year's agreement.
Travelling with Mrs Clinton is also the Obama administration's climate envoy Todd Stern.
The US House of Representatives last month passed a bill which imposes trade restrictions on countries which do not sign up to a carbon emissions cap.
The bill now moves to the Senate, but it is a source of concern for developing countries like India and China, which have refused to commit to emissions cuts unless developed nations present sufficient targets themselves.
Terror commemoration
In an interview with CNN-IBN, Mrs Clinton said that she was looking at "how together we can make the fight against climate change a win-win proposition".
"Certainly, you will not hear from me or President Obama or our administration any desire to prevent the continuing development of India. But we also understand the grave threat posed by climate change to coastal countries like India that will be on the front lines of the devastation likely to be reaped if we do not rein in the increasing temperature that is being recorded."
Before the political discussions in Delhi, Mrs Clinton is spending two days in Mumbai where she will hold meetings with business leaders, women activists and promoters of education initiatives.
The secretary of state is very keen on "people-to-people" diplomacy and usually holds town hall events and meetings with civil society leaders on foreign visits.
Her schedule on this trip is lighter than usual, however, as she tries to fit in several sessions a day of physiotherapy to recover from a broken elbow.
But Mrs Clinton will also be attending a small commemoration ceremony for the Mumbai terror attacks which left more than 170 people dead in November 2008.
Mrs Clinton is staying at the famous, century-old Taj Mahal Palace, the luxurious hotel which was targeted in the attacks and is still being refurbished.
The Indian Express newspaper said that the choice of hotel was a "gesture of solidarity with India against terrorism".
Pakistan admitted the attacks were planned on its soil. And so while India's ties with Pakistan are not officially on the agenda, the issue cannot be avoided.
The two neighbours have just held rare talks, after the Mumbai attacks sent their ties into the deep freeze.
For Washington, there is a lot riding on that as well - the US is embroiled in a battle against al-Qaeda in Afghanistan, which uses Pakistan as a support base.
Mrs Clinton is likely to push in private for a smoothing of Pakistani-Indian ties and, in her India Times opinion piece, she urged Delhi to join Washington in supporting Pakistan's fight against radical militants.