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The current phase of quantum computing is in the Noisy Intermediate-Scale Quantum (NISQ) era. On NISQ devices, two-qubit gates such as CNOTs are much noisier than single-qubit gates, so it is essential to minimize their count. Quantum circuit synthesis is a process of decomposing an arbitrary unitary into a sequence of quantum gates, and can be used as an optimization tool to produce shorter circuits to improve overall circuit fidelity. However, the time-to-solution of synthesis grows exponentially with the number of qubits. As a result, synthesis is intractable for circuits on a large qubit scale. In this paper, we propose a hierarchical, block-by-block optimization framework, QGo, for quantum circuit optimization. Our approach allows an exponential cost optimization to scale to large circuits. QGo uses a combination of partitioning and synthesis: 1) partition the circuit into a sequence of independent circuit blocks; 2) re-generate and optimize each block using quantum synthesis; and 3) re-compose the final circuit by stitching all the blocks together. We perform our analysis and show the fidelity improvements in three different regimes: small-size circuits on real devices, medium-size circuits on noise simulations, and large-size circuits on analytical models. Using a set of NISQ benchmarks, we show that QGo can reduce the number of CNOT gates by 29.9% on average and up to 50% when compared with industrial compilers such as t|ket>. When executed on the IBM Athens system, shorter depth leads to higher circuit fidelity. We also demonstrate the scalability of our QGo technique to optimize circuits of 60+ qubits. Our technique is the first demonstration of successfully employing and scaling synthesis in the compilation toolchain for large circuits. Overall, our approach is robust for direct incorporation in production compiler toolchains.